scholarly journals The Caenorhabditis elegans HAM-1 protein modifies G protein signaling and membrane extension to reverse the polarity of asymmetric cell division

2018 ◽  
Author(s):  
Jerome Teuliere ◽  
Gian Garriga
Keyword(s):  
Caenorhabditis Elegans ◽  
G Protein ◽  
Cell Fate ◽  
Daughter Cell ◽  
Asymmetric Cell Division ◽  
Opposite Polarity ◽  
Posterior Cortex ◽  
Membrane Extension ◽  
Asymmetric Divisions ◽  
Dependent Mechanism

Asymmetric divisions often produce daughter cells that differ in both fate and size. The Caenorhabditis elegans HAM-1 protein regulates both daughter cell fate and daughter cell size asymmetry (DCSA) in a subset of asymmetric divisions. Here we focus on the divisions of the Q.a and Q.p neuroblasts, which use distinct mechanisms to divide with opposite polarity. Q.a divides by a ham-1-dependent, spindle-independent, myosin-dependent mechanism to produce a smaller anterior daughter that dies, whereas Q.p divides by a ham-1-independent, spindle-dependent, myosin-independent mechanism to produce a smaller posterior daughter that dies. Despite these differences, we found that membrane extension at the posterior of Q.a and at the anterior of Q.p promoted DCSA in these cells by a Wiscott-Aldrich protein (WASp)-dependent mechanism and that in ham-1 mutant Q.a divisions, the polarity of this extension was reversed. In addition, the spindle moved posteriorly during the Q.a division in a ham-1 mutant, a phenotype normally exhibited by Q.p. We found that this spindle movement in wild-type Q.p divisions required Gα proteins that promote spindle movement in other asymmetric divisions, and GPR-1, a protein involved in linking G proteins to microtubule asters, localized to the posterior cortex of Q.p. Genetic interactions suggest that ham-1 mutant Q.a divisions also require Gα proteins function to divide with a reversed polarity. The transformation of Q.a to Q.p-like polarity in the ham-1 mutant, however, appeared incomplete: ham-1 loss did not alter the asymmetric localization of the non-muscle myosin NMY-2 to the anterior cortex of Q.a. A GFP tagged ham-1 transgene revealed that Q.a but not Q.p expressed ham-1. Finally, we show that HAM-1 has both cortical and nuclear functions in Q,a DCSA. We propose a model where HAM-1 modifies a default Q.p-type polarity by localizing WASp function to the posterior Q.a membrane and by interfering with G-protein mediated spindle movement.

scholarly journals PAR-3 and PAR-1 Inhibit LET-99 Localization to Generate a Cortical Band Important for Spindle Positioning in Caenorhabditis elegans Embryos

2007 ◽  
Vol 18 (11) ◽  
pp. 4470-4482 ◽  
Author(s):  
Jui-Ching Wu ◽  
Lesilee S. Rose
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Protein Signaling ◽  
Posterior Cortex ◽  
Par Proteins ◽  
Anterior Cortex ◽  
Spindle Positioning ◽  
High Let ◽  
Fate Determinants ◽  
Cell Fate Determinants

The conserved PAR proteins are localized in asymmetric cortical domains and are required for the polarized localization of cell fate determinants in many organisms. In Caenorhabditis elegans embryos, LET-99 and G protein signaling act downstream of the PARs to regulate spindle positioning and ensure asymmetric division. PAR-3 and PAR-2 localize LET-99 to a posterior cortical band through an unknown mechanism. Here we report that LET-99 asymmetry depends on cortically localized PAR-1 and PAR-4 but not on cytoplasmic polarity effectors. In par-1 and par-4 embryos, LET-99 accumulates at the entire posterior cortex, but remains at low levels at the anterior cortex occupied by PAR-3. Further, PAR-3 and PAR-1 have graded cortical distributions with the highest levels at the anterior and posterior poles, respectively, and the lowest levels of these proteins correlate with high LET-99 accumulation. These results suggest that PAR-3 and PAR-1 inhibit the localization of LET-99 to generate a band pattern. In addition, PAR-1 kinase activity is required for the inhibition of LET-99 localization, and PAR-1 associates with LET-99. Finally, examination of par-1 embryos suggests that the banded pattern of LET-99 is critical for normal posterior spindle displacement and to prevent spindle misorientation caused by cell shape constraints.

scholarly journals Sanpodo controls sensory organ precursor fate by directing Notch trafficking and binding γ-secretase

2013 ◽  
Vol 201 (3) ◽  
pp. 439-448 ◽  
Author(s):  
Alok Upadhyay ◽  
Vasundhara Kandachar ◽  
Diana Zitserman ◽  
Xin Tong ◽  
Fabrice Roegiers
Keyword(s):  
Notch Signaling ◽  
Cell Fate ◽  
Daughter Cell ◽  
Asymmetric Cell Division ◽  
Notch Receptor ◽  
Receptor Internalization ◽  
Sensory Organ ◽  
Cell Fates ◽  
Cellular Context ◽  
Sensory Organ Precursor

In Drosophila peripheral neurogenesis, Notch controls cell fates in sensory organ precursor (SOP) cells. SOPs undergo asymmetric cell division by segregating Numb, which inhibits Notch signaling, into the pIIb daughter cell after cytokinesis. In contrast, in the pIIa daughter cell, Notch is activated and requires Sanpodo, but its mechanism of action has not been elucidated. As Sanpodo is present in both pIIa and pIIb cells, a second role for Sanpodo in regulating Notch signaling in the low-Notch pIIb cell has been proposed. Here we demonstrate that Sanpodo regulates Notch signaling levels in both pIIa and pIIb cells via distinct mechanisms. The interaction of Sanpodo with Presenilin, a component of the γ-secretase complex, was required for Notch activation and pIIa cell fate. In contrast, Sanpodo suppresses Notch signaling in the pIIb cell by driving Notch receptor internalization. Together, these results demonstrate that a single protein can regulate Notch signaling through distinct mechanisms to either promote or suppress signaling depending on the local cellular context.

scholarly journals The polarity-induced force imbalance inCaenorhabditis elegansembryos is caused by asymmetric binding rates of dynein to the cortex

2018 ◽  
Vol 29 (26) ◽  
pp. 3093-3104 ◽  
Author(s):  
Ruddi Rodriguez-Garcia ◽  
Laurent Chesneau ◽  
Sylvain Pastezeur ◽  
Julien Roul ◽  
Marc Tramier ◽  
...  
Keyword(s):  
Cell Fate ◽  
Asymmetric Cell Division ◽  
Molecular Motor ◽  
Dependent Manner ◽  
Mitotic Progression ◽  
Posterior Cortex ◽  
Antibody Staining ◽  
Pulling Forces ◽  
Fate Determinants ◽  
Cell Fate Determinants

During asymmetric cell division, the molecular motor dynein generates cortical pulling forces that position the spindle to reflect polarity and adequately distribute cell fate determinants. In Caenorhabditis elegans embryos, despite a measured anteroposterior force imbalance, antibody staining failed to reveal dynein enrichment at the posterior cortex, suggesting a transient localization there. Dynein accumulates at the microtubule plus ends, in an EBP-2EB–dependent manner. This accumulation, although not transporting dynein, contributes modestly to cortical forces. Most dyneins may instead diffuse to the cortex. Tracking of cortical dynein revealed two motions: one directed and the other diffusive-like, corresponding to force-generating events. Surprisingly, while dynein is not polarized at the plus ends or in the cytoplasm, diffusive-like tracks were more frequently found at the embryo posterior tip, where the forces are higher. This asymmetry depends on GPR-1/2LGNand LIN-5NuMA, which are enriched there. In csnk-1(RNAi) embryos, the inverse distribution of these proteins coincides with an increased frequency of diffusive-like tracks anteriorly. Importantly, dynein cortical residence time is always symmetric. We propose that the dynein-binding rate at the posterior cortex is increased, causing the polarity-reflecting force imbalance. This mechanism of control supplements the regulation of mitotic progression through the nonpolarized dynein detachment rate.

scholarly journals Roles of Actin in the Morphogenesis of the Early Caenorhabditis elegans Embryo

2020 ◽  
Vol 21 (10) ◽  
pp. 3652
Author(s):  
Dureen Samandar Eweis ◽  
Julie Plastino
Keyword(s):  
Cell Division ◽  
Caenorhabditis Elegans ◽  
Asymmetric Cell Division ◽  
Cell Types ◽  
Actin Dynamics ◽  
Actin Binding ◽  
Asymmetric Cell Divisions ◽  
C Elegans ◽  
Asymmetric Divisions ◽  
Different Cell Types

The cell shape changes that ensure asymmetric cell divisions are crucial for correct development, as asymmetric divisions allow for the formation of different cell types and therefore different tissues. The first division of the Caenorhabditis elegans embryo has emerged as a powerful model for understanding asymmetric cell division. The dynamics of microtubules, polarity proteins, and the actin cytoskeleton are all key for this process. In this review, we highlight studies from the last five years revealing new insights about the role of actin dynamics in the first asymmetric cell division of the early C. elegans embryo. Recent results concerning the roles of actin and actin binding proteins in symmetry breaking, cortical flows, cortical integrity, and cleavage furrow formation are described.

scholarly journals MAP Kinase Signaling Antagonizes PAR-1 Function During Polarization of the Early Caenorhabditis elegans Embryo

Genetics ◽  
2009 ◽  
Vol 183 (3) ◽  
pp. 965-977 ◽  
Author(s):  
Annina C. Spilker ◽  
Alexia Rabilotta ◽  
Caroline Zbinden ◽  
Jean-Claude Labbé ◽  
Monica Gotta
Keyword(s):  
Cell Division ◽  
Caenorhabditis Elegans ◽  
Map Kinase ◽  
Cell Fate ◽  
Asymmetric Cell Division ◽  
Asymmetric Distribution ◽  
Kinase Signaling ◽  
C Elegans ◽  
Link Type ◽  
Map Kinase Signaling

PAR proteins (partitioning defective) are major regulators of cell polarity and asymmetric cell division. One of the par genes, par-1, encodes a Ser/Thr kinase that is conserved from yeast to mammals. In Caenorhabditis elegans, par-1 governs asymmetric cell division by ensuring the polar distribution of cell fate determinants. However the precise mechanisms by which PAR-1 regulates asymmetric cell division in C. elegans remain to be elucidated. We performed a genomewide RNAi screen and identified six genes that specifically suppress the embryonic lethal phenotype associated with mutations in par-1. One of these suppressors is mpk-1, the C. elegans homolog of the conserved mitogen activated protein (MAP) kinase ERK. Loss of function of mpk-1 restored embryonic viability, asynchronous cell divisions, the asymmetric distribution of cell fate specification markers, and the distribution of PAR-1 protein in par-1 mutant embryos, indicating that this genetic interaction is functionally relevant for embryonic development. Furthermore, disrupting the function of other components of the MAPK signaling pathway resulted in suppression of par-1 embryonic lethality. Our data therefore indicates that MAP kinase signaling antagonizes PAR-1 signaling during early C. elegans embryonic polarization.

scholarly journals Distinct roles of Gαi and Gβ13F subunits of the heterotrimeric G protein complex in the mediation of Drosophila neuroblast asymmetric divisions

2003 ◽  
Vol 162 (4) ◽  
pp. 623-633 ◽  
Author(s):  
Fengwei Yu ◽  
Yu Cai ◽  
Rachna Kaushik ◽  
Xiaohang Yang ◽  
William Chia
Keyword(s):  
G Protein ◽  
Cell Fate ◽  
Protein Complex ◽  
Complex Function ◽  
Asymmetric Division ◽  
Loss Of Function ◽  
Daughter Cells ◽  
Asymmetric Divisions ◽  
Fate Determinants ◽  
Cell Fate Determinants

The asymmetric division of Drosophila neuroblasts involves the basal localization of cell fate determinants and the generation of an asymmetric, apicobasally oriented mitotic spindle that leads to the formation of two daughter cells of unequal size. These features are thought to be controlled by an apically localized protein complex comprising of two signaling pathways: Bazooka/Drosophila atypical PKC/Inscuteable/DmPar6 and Partner of inscuteable (Pins)/Gαi; in addition, Gβ13F is also required. However, the role of Gαi and the hierarchical relationship between the G protein subunits and apical components are not well defined. Here we describe the isolation of Gαi mutants and show that Gαi and Gβ13F play distinct roles. Gαi is required for Pins to localize to the cortex, and the effects of loss of Gαi or pins are highly similar, supporting the idea that Pins/Gαi act together to mediate various aspects of neuroblast asymmetric division. In contrast, Gβ13F appears to regulate the asymmetric localization/stability of all apical components, and Gβ13F loss of function exhibits phenotypes resembling those seen when both apical pathways have been compromised, suggesting that it acts upstream of the apical pathways. Importantly, our results have also revealed a novel aspect of apical complex function, that is, the two apical pathways act redundantly to suppress the formation of basal astral microtubules in neuroblasts.

scholarly journals Drosophila neuroblasts as a new model for the study of stem cell self-renewal and tumour formation

2014 ◽  
Vol 34 (4) ◽  
Author(s):  
Song Li ◽  
Hongyan Wang ◽  
Casper Groth
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Daughter Cell ◽  
Asymmetric Cell Division ◽  
Cell Fate Specification ◽  
Larval Brain ◽  
Self Renewal ◽  
Intrinsic Factors ◽  
Tumour Formation

Drosophila larval brain stem cells (neuroblasts) have emerged as an important model for the study of stem cell asymmetric division and the mechanisms underlying the transformation of neural stem cells into tumour-forming cancer stem cells. Each Drosophila neuroblast divides asymmetrically to produce a larger daughter cell that retains neuroblast identity, and a smaller daughter cell that is committed to undergo differentiation. Neuroblast self-renewal and differentiation are tightly controlled by a set of intrinsic factors that regulate ACD (asymmetric cell division). Any disruption of these two processes may deleteriously affect the delicate balance between neuroblast self-renewal and progenitor cell fate specification and differentiation, causing neuroblast overgrowth and ultimately lead to tumour formation in the fly. In this review, we discuss the mechanisms underlying Drosophila neural stem cell self-renewal and differentiation. Furthermore, we highlight emerging evidence in support of the notion that defects in ACD in mammalian systems, which may play significant roles in the series of pathogenic events leading to the development of brain cancers.

scholarly journals Differential functions of G protein and Baz–aPKC signaling pathways in Drosophila neuroblast asymmetric division

2004 ◽  
Vol 164 (5) ◽  
pp. 729-738 ◽  
Author(s):  
Yasushi Izumi ◽  
Nao Ohta ◽  
Asako Itoh-Furuya ◽  
Naoyuki Fuse ◽  
Fumio Matsuzaki
Keyword(s):  
Signaling Pathways ◽  
G Protein ◽  
Cell Fate ◽  
Dominant Role ◽  
Spindle Orientation ◽  
Mitotic Spindles ◽  
Asymmetric Divisions ◽  
Fate Determinants ◽  
Cell Fate Determinants

Drosophila melanogaster neuroblasts (NBs) undergo asymmetric divisions during which cell-fate determinants localize asymmetrically, mitotic spindles orient along the apical–basal axis, and unequal-sized daughter cells appear. We identified here the first Drosophila mutant in the Gγ1 subunit of heterotrimeric G protein, which produces Gγ1 lacking its membrane anchor site and exhibits phenotypes identical to those of Gβ13F, including abnormal spindle asymmetry and spindle orientation in NB divisions. This mutant fails to bind Gβ13F to the membrane, indicating an essential role of cortical Gγ1–Gβ13F signaling in asymmetric divisions. In Gγ1 and Gβ13F mutant NBs, Pins–Gαi, which normally localize in the apical cortex, no longer distribute asymmetrically. However, the other apical components, Bazooka–atypical PKC–Par6–Inscuteable, still remain polarized and responsible for asymmetric Miranda localization, suggesting their dominant role in localizing cell-fate determinants. Further analysis of Gβγ and other mutants indicates a predominant role of Partner of Inscuteable–Gαi in spindle orientation. We thus suggest that the two apical signaling pathways have overlapping but different roles in asymmetric NB division.

scholarly journals Spindle assembly checkpoint strength is linked to cell fate in the Caenorhabditis elegans embryo

2018 ◽  
Vol 29 (12) ◽  
pp. 1435-1448 ◽  
Author(s):  
Abigail R. Gerhold ◽  
Vincent Poupart ◽  
Jean-Claude Labbé ◽  
Paul S. Maddox
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Size ◽  
Cell Fate ◽  
Genome Stability ◽  
Spindle Assembly Checkpoint ◽  
Asymmetric Cell Division ◽  
Spindle Assembly ◽  
Microtubule Attachment ◽  
Anaphase Onset ◽  
The Difference

The spindle assembly checkpoint (SAC) is a conserved mitotic regulator that preserves genome stability by monitoring kinetochore–microtubule attachments and blocking anaphase onset until chromosome biorientation is achieved. Despite its central role in maintaining mitotic fidelity, the ability of the SAC to delay mitotic exit in the presence of kinetochore–microtubule attachment defects (SAC “strength”) appears to vary widely. How different cellular aspects drive this variation remains largely unknown. Here we show that SAC strength is correlated with cell fate during development of Caenorhabditis elegans embryos, with germline-fated cells experiencing longer mitotic delays upon spindle perturbation than somatic cells. These differences are entirely dependent on an intact checkpoint and only partially attributable to differences in cell size. In two-cell embryos, cell size accounts for half of the difference in SAC strength between the larger somatic AB and the smaller germline P1 blastomeres. The remaining difference requires asymmetric cytoplasmic partitioning downstream of PAR polarity proteins, suggesting that checkpoint-regulating factors are distributed asymmetrically during early germ cell divisions. Our results indicate that SAC activity is linked to cell fate and reveal a hitherto unknown interaction between asymmetric cell division and the SAC.

scholarly journals Wnt Signaling and a Hox Protein Cooperatively Regulate PSA-3/Meis to Determine Daughter Cell Fate after Asymmetric Cell Division in C. elegans

2006 ◽  
Vol 11 (1) ◽  
pp. 105-115 ◽  
Author(s):  
Yukinobu Arata ◽  
Hiroko Kouike ◽  
Yanping Zhang ◽  
Michael A. Herman ◽  
Hideyuki Okano ◽  
...  
Keyword(s):  
Cell Division ◽  
Wnt Signaling ◽  
Cell Fate ◽  
Daughter Cell ◽  
Asymmetric Cell Division ◽  
C Elegans ◽  
Hox Protein
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